Trial Information

A Phase 2 Study of Fludarabine, Cytarabine, Filgrastim and Idarubicin in Newly Diagnosed Core Binding Factor Associated Acute Myelogenous Leukemia

The Study Drugs:

Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic
material of cells). This may increase the likelihood of the cells dying.

Cytarabine is designed to insert itself into DNA and stop the DNA from repairing itself.

Filgrastim promotes the growth of white blood cells, which help to fight infections.

Decitabine and Idarubicin are designed to damage the DNA (the genetic material) of cells,
which may cause cancer cells to die.

Parts of the Study:

There will be 2 parts to this study. The first part of the study is called induction
therapy. During induction, the study doctor will try to get rid of the leukemia cells from
your bone marrow. If induction causes the leukemia cells to be removed from your bone marrow
and your blood counts return to normal, you will be in remission. Induction usually lasts
4-6 weeks.

If you are in remission, you will begin the second part of the study, called post-remission
therapy. You will receive up to 4-6 cycles (1 cycle every 4-6 weeks) of post-remission
therapy, depending on your blood counts. Each study cycle lasts 4-6 weeks.

Study Drug Administration:

If you are found to be eligible to take part in this study, during induction therapy, you
will be given fludarabine and cytarabine through a needle in your vein every day, for 5 days
in a row (Days 1-5). You will receive fludarabine over 30 minutes and cytarabine over 4
hours.

Filgrastim will be given one time daily as an injection just under the skin starting on the
day before you receive fludarabine and cytarabine, and you will continue to receive
filgrastim one time daily until your white blood cell count is near normal.

You will receive idarubicin through a needle in your vein over 30 minutes on Days 3 and 4
right after you receive fludarabine.

During post-remission therapy, you will receive fludarabine and cytarabine for 3 days (Days
1-3) instead of 5 days. You will receive idarubicin at the same dose as given during
induction therapy on Days 2 and 3. You will receive idarubicin one time during Cycles 3-6
during post-remission therapy. You will receive filgrastim one time on the day before each
post-remission cycle.

During post-remission therapy, you may begin receiving decitabine instead of fludarabine,
cytarabine, filgrastim, and/or idarubicin if you are 60 years or older, or if you have had
intolerable side effects. If the doctor thinks it is in your best interest, you will begin
receiving decitabine infusions over 1 hour, for 5 days in a row, every 4-6 weeks for up to
12 cycles. The doctor will discuss this with you.

Study Visits:

During induction therapy, blood (about 2 teaspoons) will be drawn at least once a week for
routine testing.

After 3 weeks (Between Days 18-24), you will have a bone marrow aspirate to check the status
of the disease. If the leukemia cells are not completely gone from your bone marrow by the
end of 3 weeks, your study doctor may decide to repeat the test.

If the repeat bone marrow aspirate shows that you are not in remission, your study doctor
may decide to give you another cycle of induction therapy.

Once you begin post-remission therapy, you will have the following tests and procedures:

- You will have a physical exam, including measurement of your vital signs, including
your weight.

- You will be asked how well you are able to perform the normal activities of daily
living (performance status).

- Blood (about 2 teaspoons) will be drawn for routine blood tests.

At Months 4 and 7, you will have a bone marrow aspirate to check the status of the disease.

Part of the bone marrow sample collected at these bone marrow aspirations will be sent to
the M. D. Anderson molecular lab for testing.

If your study doctor thinks it is necessary, you may have a bone marrow aspirate after the
first 7 months to check the status of the disease.

Length of Study:

You will be on study for one cycle of induction therapy and up to 6 cycles of post-remission
therapy. You will be taken off study if the disease gets worse or intolerable side effects
occur.

Long-term follow up:

You will have blood (about 2 teaspoons) drawn for routine testing every 6 months for 2 years
after the study.

This is an investigational study. Cytarabine is FDA approved and commercially available for
the treatment of AML. Fludarabine is FDA approved and commercially available for the
treatment of chronic lymphocytic leukemia (CLL). Filgrastim is FDA approved and
commercially available to treat fever associated with low white cell counts in patients with
AML. Idarubicin is FDA approved and commercially available for the treatment of acute
leukemias, lymphomas, Hodgkin's disease and breast cancer. At this time, their use in
combination is for research purposes only.

Decitabine is FDA approved for treatment of myelodysplastic syndrome and is commercially
available.

Up to 102 patients will take part in this study. All will be enrolled at M. D. Anderson.